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Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence

Eren, Remzi Onur
Reverte, Marta
Rossi, Matteo
Hartley, Mary-Anne
Castiglioni, Patrik
Prevel, Florence
Martin, Ricardo
Desponds, Chantal
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Published in Cell Host & Microbe. 2016, vol. 20, no. 3, p. 318-328
Abstract Some strains of the protozoan parasite Leishmania guyanensis (L.g) harbor a viral endosymbiont called Leishmania RNA virus 1 (LRV1). LRV1 recognition by TLR-3 increases parasite burden and lesion swelling in vivo. However, the mechanisms by which anti-viral innate immune responses affect parasitic infection are largely unknown. Upon investigating the mammalian host's response to LRV1, we found that miR-155 was singularly and strongly upregulated in macrophages infected with LRV1+ L.g when compared to LRV1- L.g. LRV1-driven miR-155 expression was dependent on TLR-3/TRIF signaling. Furthermore, LRV1-induced TLR-3 activation promoted parasite persistence by enhancing macrophage survival through Akt activation in a manner partially dependent on miR-155. Pharmacological inhibition of Akt resulted in a decrease in LRV1-mediated macrophage survival and consequently decreased parasite persistence. Consistent with these data, miR-155-deficient mice showed a drastic decrease in LRV1-induced disease severity, and lesional macrophages from these mice displayed reduced levels of Akt phosphorylation.
Keywords AnimalsCell SurvivalDisease Models, AnimalImmunity, InnateLeishmania guyanensis/pathogenicity/physiology/virologyLeishmaniasis, Mucocutaneous/parasitology/pathologyLeishmaniavirus/immunologyMacrophages/immunology/parasitologyMiceMice, KnockoutMicroRNAs/metabolismProto-Oncogene Proteins c-akt/metabolismToll-Like Receptor 3/metabolism
PMID: 27593513
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Article (Author postprint) (928 Kb) - public document Free access
Research group Groupe Reith Walter (pathologie et immunologie) (282)
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EREN, Remzi Onur et al. Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence. In: Cell Host & Microbe, 2016, vol. 20, n° 3, p. 318-328. https://archive-ouverte.unige.ch/unige:99854

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Deposited on : 2017-11-30

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